We report a case of a 26-year-old man with no signiﬁcant medical history, who presented with fatigue, pruritus, jaundice, dark urine and clay colored stool for one month. He had been taking methyl-1-etiochoenolol-epietiocholanolone, an androgenic anabolic steroid (AAS). He was initially found to have a total bilirubin (Tbili) of 6 mg/dL. He discontinued the AAS but the patients’ symptoms worsened and Tbili increased to 36 mg/d. This prompted inpatient management of his drug-induced liver injury (DILI). Molecular adsorbent recirculating system (MARS) is an extracorporeal liver support system that replaces the detoxiﬁcation function of the liver. The patient was initiated on a 4-day trial of MARS therapy. Over the course of his therapy, he clinically improved and his Tbili decreased to 20.7 mg/dL. At follow-up, his symptoms resolved and Tbili was 3.3 mg/dl. This case demonstrates the efﬁcacy of MARS in treating severe cholestatic DILI refractory to standard medical therapy. and clay colored stools for 1 month. The patient had been tak- INTRODUCTION ing methyl-1-etiochoenolol-epietiocholanolone, an androgenic Acute liver injury (ALI) is associated with high mortality. Drug- anabolic steroid (AAS). induced liver injury (DILI) is responsible for ~50% of cases of ALI in Initially, at an outpatient clinic he was found to have a total the USA [1, 2]. Extracorporeal liver assist devices can help achieve bilirubin (Tbili) of 6 mg/dl. He was advised to discontinue the hemodynamic stability while patients with ALI await liver trans- AAS. He discontinued the AAS but the patients’ symptoms wor- plant, with the possibility of hepatic regeneration and recovery. sened. Repeat blood work 2 weeks later showed a Tbili of Molecular Adsorbent Recirculating System (MARS) is an extracor- 32.5 mg/d, which prompted inpatient management. poreal liver support system that replaces the detoxiﬁcation func- The patient denied use of other hepatotoxic drugs, herbal tion of the liver using an albumin-enriched dialysate to aid in the supplements, tobacco, illicit drugs or alcohol. He had a similar elimination of albumin-bound and water-soluble toxins . episode 5 years ago; he had been taking a similar AAS and developed mild jaundice, which resolved spontaneously once he discontinued the AAS. CASE REPORT On exam, his vital signs were normal. He was extensively A 26-year-old Caucasian male with no signiﬁcant past medical jaundiced, had a normal mental status without asterixis, and normal cardio-respiratory and abdominal exam without ascites history presented with fatigue, pruritus, jaundice, dark urine Received: July 23, 2017. Revised: September 30, 2017. Accepted: October 10, 2017 © The Author 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact email@example.com Downloaded from https://academic.oup.com/omcr/article-abstract/2018/1/omx077/4782679 by Ed 'DeepDyve' Gillespie user on 16 March 2018 2 J. Eapen et al. or hepatomegaly. Liver biochemistries revealed aspartate ami- notransferase (AST) 67 U/l, alanine transaminase (ALT) 106 U/L, alkaline phosphatase 166 U/l, Tbili 36 mg/dl, and international normalized ratio (INR) 0.95. Complete blood cell count (CBC) and Renal Function Panel (RFP) were normal. An extensive infectious, autoimmune, and metabolic work was negative. His abdominal ultrasound was normal. At this stage, he was initiated on a 4-day trial of MARS ther- apy due to refractory hyperbilirubinemia after standard med- ical therapy (SMT). By day 3 of MARS therapy his pruritus, fatigue, hemoglobinuria and jaundice improved. Liver biochem- istries at that time revealed AST 95 U/l, ALT 147 U/l, alkaline phosphatase 166 U/l, Tbili 24.3 mg/dl and INR 1.01. CBC and RFP remained normal. Over the course of his therapy, he remained hemodynamic- ally stable, clinically improved and his Tbili decreased to 20.7 mg/dl. A percutaneous liver biopsy was performed showing severe cholestasis with bile duct injury/inﬂammation and hep- atocyte injury without steatosis (Fig. 1), consistent with DILI. Patient was discharge with outpatient follow-up. At 2 months follow-up he ceased taking AAS and noted a reso- Figure 1: Centrizonal parenchyma demonstrating severe cholestasis with form- lution of his fatigue, jaundice, pruritus, and abnormal stool and ation of cholestatic rosettes, mild lymphocytic inﬂammation, reactive changes urine color. Labs showed AST 56, ALT 104 and Tbili 3.3 mg/dl. in hepatocytes, and an acidophil body (apoptotic hepatocyte). Hematoxylin and eosin stain, 400x overall magniﬁcation. Abnormal Liver Function Tests Obtain detailed history and physical, and medication list (including Herbal and Dietary supplements) Calculate R value* R Value = Serum (ALT/ALT ULN) + (Alk P/Alk P ULN) R value > 5 2 < R value < 5 R value < 2 (Hepatocelluar) (Mixed) (Cholestatic) Initial Investigation: Acute viral Initial Investigation: Acute viral Initial Investigation: Imaging hepatitis and autoimmune hepatitis (abdominal ultrasound, computerized hepatitis and autoimmune hepatitis serologies, imaging studies (e.g., serologies, imaging studies (e.g., tomography) abdominal ultrasound, computerized abdominal ultrasound, computerized Secondary Investigation: Case by case tomography) tomography) basis, Cholangiography (either Secondary Investigation: Case by case endoscopic or MR based), serologies for Secondary Investigation: Case by case basis, ceruloplasmin, serologies for less basis, ceruloplasmin, serologies for less primary biliary cirrhosis, liver biopsy common viruses, liver biopsy common viruses, liver biopsy Assessment of data, causality assessment and diagnosis: 1. Assessment of data: a. Completeness: Reasonable exclusion of all non DILI etiologies b. Literature review by use of LiverTox and Pubmed 2. Clinical judgement for inal DILI diagnosis 3. Expert Consultation if diagnosis remains uncertain Figure 2: Flow chart for the diagnosis of DILI . Downloaded from https://academic.oup.com/omcr/article-abstract/2018/1/omx077/4782679 by Ed 'DeepDyve' Gillespie user on 16 March 2018 The efﬁcacy of extracorporeal liver support 3 demonstrates the efﬁcacy of MARS in patients with severe bile Table 1: Side effects of anabolic steroids by organ system acid nephropathy and other forms of renal dysfunction more Organ Systems DISEASES commonly seen with AAS DILI [9, 10]. Other case reports and series have reported an improvement in both symptoms LIVER Hepatitis, cholestatic hepatitis, Peliosis (including jaundice, pruritus and confusion) and biochemical hepatis, hepatic adenoma, Hepatocellular parameters after 3–4 sessions of MARS therapy. carcinoma, Focal nodular hyperplasia In regards to acute liver failure (ALF) the use of MARS has CARDIAC Left ventricular hypertrophy, hypertension, not been fully established. MARS is a useful tool that has been myocardial infarction, arrhythmias shown to stabilize clinical conditions in ALF patients awaiting RENAL Focal segmental glomerulosclerosis, cholemic nephrosis transplant, and facilitate hepatic regeneration. Several clinical NEUROPSYCHIATRIC Depression, anxiety, addiction potential trials have concluded MARS as a reasonable tool in ALF patients’ by reducing bilirubin levels, improving hemodynamic status, renal dysfunction and hepatic encephalopathy [16–18]. A multicenter, randomized, controlled trial involving patients DISCUSSION with acute liver failure showed no survival beneﬁt. DILI presents a challenging diagnosis for many physicians as Although survival beneﬁt has not been proven, it has a the its presentation can vary anywhere between acute fulminant potential to beneﬁt speciﬁc patient subgroups. hepatic failure to mild hepatitis. The American College of Gastroenterology created guidelines to help clinicians with the CONCLUSION diagnosis of DILI (Fig. 2). DILI is a diagnosis of exclusion, in MARS has been reported to stabilize clinical parameters in which proper history and correlating the use of the drug in patients with DILI and DILI associated ALI patients, with a goal question to the onset of the symptoms and lab abnormalities is to bridge the patient to spontaneous recovery or liver trans- key . plant. In the setting of cholestatic liver injury, MARS may be of DILI can be due to numerous medications and/or drugs, particular beneﬁt given its ability to extract bilirubin, which is both prescription and over the counter with >1000 estimated an albumin-bound toxin. This case demonstrates the efﬁcacy medications and supplements being implicated [6, 7]. DILI of MARS in treating severe cholestatic DILI due to AAS that was accounts for ~10% of all cases of acute hepatitis , and it is the refractory to standard medical therapy. most common cause of ALI in the USA [1, 9]. In this case, the patients’ previous history of similar symptoms after using AAS with use of another AAS, and hyperbilirubinemia pointed CONFLICT OF INTEREST STATEMENT towards the diagnosis of DILI, with a percutaneous liver biopsy Informed consent was obtained for publication of this case conﬁrming the diagnosis. report. This case report in part has been previously presented AAS have grown tremendously in popularity especially as an abstract poster at American College of Gastroenterology amongst athletes and bodybuilders. Robles et al. reports a 3- 2015 Annual Scientiﬁc Meeting. It has thus been expanded and fold increase in the number of AAS induced DILI cases over 1 enriched from the abstract version. decade, a total growth from 1 to 8% between 2000 and 2013 [10, 11]. Consequentially, this upsurge of AAS use has not AUTHORS’ ROLES only led to increasing cases of DILI, but also to multi-organ side effects including cardiac dysfunction, neuropsychiatric J.E. and R.A. drafted, reviewed and edited the manuscript. R.S. disorders, and renal impairment (Table 1)[5, 10–14]. AAS DILI reviewed and edited the manuscript. R.A. is the article presents predominantly as cholestasis, but hepatocellular guarantor. damage or both patterns can be seen . 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Published: Jan 1, 2018
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